For Health Officials and School Boards: Asymptomatic Measles Infection is Real

There was a time when it was openly recognized that vaccinated individuals could become infected with wild-type measles.  These infections are called subclinical infections (aka asymptomatic infections). We don’t talk about that very much anymore. In fact, two days ago I had a conference call with a high-ranking health official at the NYC Health Commission who claimed that it does not happen – specifically, that official stated that subclinical infections do not occur.

Given that this person is so obviously misinformed, I thought I would provide a literature resource for those who might not realize this reality: vaccinated individuals can, and have always, been known to be able to be infected with wild-type measles virus.  Since this is true, the rare non-vaccinated child is not, in a highly vaccinated population, to be the primary source of new transmissions of measles.  Instead, the vaccinated individuals with subclinical infections may be driving new infections in schools. It is therefore illogical, and quite unfair, to blame unvaccinated individuals when infected asymptomatic individuals can go to school unabated.

If we are to have public health policies based on science, this science must be given due consideration; otherwise, we would have public health policies based on something other than science.  In reality, in highly vaccinated populations, measles can spread from a majority of vaccinated, to a minority of unvaccinated people, causing overt disease.  In other words, the unvaccinated merely expose the circulating measles virus, and any child with a compromised immune system may be exposed even in a fully vaccinated population.

Not all full texts are freely available online, but some are. Here are some relevant examples from the primary scientific literature.

#1. Nonclassic measles infections in an immune population exposed to measles during a college bus trip. Helfand RF https://www.ncbi.nlm.nih.gov/pubmed/?term=9829639

“Mild or asymptomatic measles infections are probably very common among measles-immune persons exposed to measles cases and may be the most common manifestation of measles during outbreaks in highly immune populations.”

#2. Current status of measles in Japan. Nakayama T, Zhou J, Fujino M. https://www.ncbi.nlm.nih.gov/pubmed/12673398

“Measles infection is considered to provide lifelong immunity after an infection and, thus, live measles vaccines also induce longterm immunity. But long-term immunity is now considered to be an effect of natural boosts via subclinical reinfection. Subclinical infection has been demonstrated by sero-conversion, but the isolation or detection of the measles virus genome was rarely demonstrated”… 

“Potential impediments to eradication include: (1) a lack of political will in some industrialized countries, (2) transmission among adults, (3) increasing urbanization and population density, (4) HIV epidemics, (5) waning immunity and the possibility of  transmission from subclinical cases, and (6) risk of unsafe injection.”

#3. Protective titres of measles neutralising antibody. Lee MS et al. https://www.ncbi.nlm.nih.gov/pubmed/11074481

“…only 1 vaccinee with HI titre #31 mIU/ml experienced typical measles symptoms and 13 vaccinees with HI titres #31 mIU/ml experienced subclinical infection.”

#4. Effect of subclinical infection on maintaining immunity against measles in vaccinated children in West Africa. Whittle HC et al. https://www.ncbi.nlm.nih.gov/pubmed/?term=10023894

“Subclinical measles occurred in 39 (45%) of 86 vaccinated children who were exposed to measles and in four (25%) of 16 unvaccinated children…”

#5. Detection of measles virus genome in lymphocytes from asymptomatic healthy children. Sonoda S, Nakayama T. https://www.ncbi.nlm.nih.gov/pubmed/11536248

“Serological confirmation of subclinical re-infection was obtained by pre-exposure in household-exposed parents who developed asymptomatic secondary immune responseswith a concomitant increase in specific IgG neutralizing test antibodies and haemagglutination inhibition titres…Subclinical infection was confirmed in adulthood.”

“In Japan, measles virus has been circulating and asymptomatic infection has occurred frequently…”

#6. The Clinical Significance of Measles: A Review Walter A. Orenstein Robert T. Perry Neal A. Halsey https://academic.oup.com/jid/article/189/Supplement_1/S4/823958

“People with inapparent subclinical measles virus infections are not known to transmit measles virus to household contacts.”

#7. Detection of measles virus genome in bone-marrow aspirates from adults. Sonoda S, Kitahara M, Nakayama T. http://www.microbiologyresearch.org/docserver/fulltext/jgv/83/10/0832485a.pdf

#8. Waning immunity and subclinical measles infections in England. Glass K, Grenfell BT. https://www.ncbi.nlm.nih.gov/pubmed/15364464

“A comparison of these cases … shows us that adding subclinical infections to the model also increases the number of clinical cases, as the subclinical infections increase the levels of circulating virus. This feature is more pronounced … because {when) vaccination
levels are higher … subclinical cases make up a greater proportion of the total cases.”

#9. Subclinical measles infection in vaccinated seropositive individuals in arctic Greenland. Pedersen IR https://www.ncbi.nlm.nih.gov/pubmed/2815970

“measles can spread from a majority of vaccinated, to a minority of unvaccinated people, causing overt disease.”

#10. Isolation of measles virus from a naturally-immune, asymptomatically re-infected individual. Vardas E, Kreis S https://www.ncbi.nlm.nih.gov/pubmed/10443793

#11. Risk analysis for measles reintroduction post global certification of eradication. Dr Ray Sanders. https://www.who.int/immunization/sage/7._Measles_post_eradication_risk_analysis.pdf

#12. Effect of subclinical infection on maintaining immunity against measles in vaccinated children in West Africa.

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(98)02364-2/fulltext

#13. Measles eradication: is it in our future? Orenstein WA, Strebel PM, Papania M, Sutter RW, Bellini WJ, Cochi SL. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1446359/

#14. The Re-Emergence of Measles in Developed Countries: Time to Develop the Next-Generation Measles Vaccines?https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3905323/

#15. Modeling the Impact of Subclinical Measles Transmission in Vaccinated Populations with Waning Immunity Mossong, J et al.  https://watermark.silverchair.com/150-11-1238.pdf

“In view of eradication, it is therefore important to investigate whether current vaccines perform well enough to prevent persistence of wild virus in highly or even fully vaccinated populations.”

#16. “Mild or asymptomatic measles infections are probably very common among measles‐immune persons exposed to measles cases, but transmission from asymptomatic cases is likely to be very rare. … However, the potential role of asymptomatic infections in maintaining transmission requires further investigation.”

https://www.who.int/immunization/sage/7._Measles_post_eradication_risk_analysis.pdf

 

15 comments

  1. My kids got “measles” after having contact with a happy bouncing 7-8 month old girl with a measles rash. My kids got sick, one after the other, but it was just about a 24 hour fever. High-ish, maybe 102.5 at the most. They definitely didn’t feel good and slept most of the way through it. And no rash, no photophobia. And lifetime immunity. Yes, I had their blood tested. POS for all 3 kids (and no not a lab error, it was sent to a big processing lab, it looks like, and they had 3 different lab numbers listed on the forms!) best, Liora. BTW this happened in China, we are so fortunate, but this is in a country with a 99.5 percent vaccine compliance rate! Thanks G-d the wild measles virus still goes around! We were truly blessed to luck into immunity like this.

  2. Do the studies below fit into this category?

    Outbreak of Measles Among Persons With Prior Evidence of Immunity, New York City, 2011
    Jennifer B. Rosen Jennifer S. Rota Carole J. Hickman Sun B. Sowers Sara Mercader Paul A. Rota William J. Bellini Ada J. Huang Margaret K. Doll Jane R. Zucker …
    https://academic.oup.com/cid/article/58/9/1205/2895266

    A measles outbreak occurred in New York City. All cases had prior evidence of measles immunity. Symptoms were consistent with measles. Laboratory results indicated secondary immune responses. This report documents measles transmission from an individual with verified secondary vaccine failure.

    Background. Measles was eliminated in the United States through high vaccination coverage and a public health system able to rapidly respond to measles. Measles may occur among vaccinated individuals, but secondary transmission from such individuals has not been documented.

    Methods. Suspected patients and contacts exposed during a measles outbreak in New York City in 2011 were investigated. Medical histories and immunization records were obtained. Cases were confirmed by detection of measles-specific immunoglobulin M and/or RNA. Tests for measles immunoglobulin G (IgG), IgG avidity, measurement of measles neutralizing antibody titers, and genotyping were performed to characterize the cases.

    Results. The index patient had 2 doses of measles-containing vaccine; of 88 contacts, 4 secondary patients were confirmed who had either 2 doses of measles-containing vaccine or a past positive measles IgG antibody. All patients had laboratory confirmation of measles infection, clinical symptoms consistent with measles, and high-avidity IgG antibody characteristic of a secondary immune response. Neutralizing antibody titers of secondary patients reached >80 000 mIU/mL 3–4 days after rash onset and that of the index was <500 mIU/mL 9 days after rash onset. No additional cases of measles occurred among 231 contacts of secondary patients.

    Conclusions. This is the first report of measles transmission from a twice-vaccinated individual with documented secondary vaccine failure. The clinical presentation and laboratory data of the index patient were typical of measles in a naive individual. Secondary patients had robust anamnestic antibody responses. No tertiary cases occurred despite numerous contacts. This outbreak underscores the need for thorough epidemiologic and laboratory investigation of suspected cases of measles regardless of vaccination status.

    Failure to reach the goal of measles elimination. Apparent paradox of measles infections in immunized persons.
    Poland GA1, Jacobson RM.
    https://www.ncbi.nlm.nih.gov/pubmed/8053748

    The Re-Emergence of Measles in Developed Countries: Time to Develop the Next-Generation Measles Vaccines?
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3905323/

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